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.1 Ribeirão Preto Jan./Feb. 2011 ORIGINAL ARTICLES Clinical application of Chamomilla recutita in phlebitis: dose response curve study1 Paula Elaine Diniz dos ReisI; Emilia Campos de CarvalhoII; Paula Carolina Pires BuenoIII; Jairo Kenupp BastosIV IRN, Ph.D. in Nursing, Adjunct Professor, Universidade de Brasília, DF, Brazil. E-mail: pdinizreis@yahoo.com IIRN, Ph.D. in Nursing, Full Professor, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, WHO Collaborating Centre for Nursing Research Development, SP, Brazil. E-mail: ecdcava@eerp.usp.br IIIPharmacy-Biochemistry, M.Sc. in Pharmaceutical Sciences E-mail: paulabueno@yahoo.com.br IVPharmacist, Ph.D. in Organic Chemistry of Natural Products, Full Professor, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, SP, Brazil. E-mail: jkbastos@fcfrp.usp.br ABSTRACT.(ClinicalTrials.gov Identifier: NCT 00989599). Descriptors: Matricaria; Phlebitis; Dose-Response Relationship, Drug. Introduction Phlebitis can be considered a temporary or permanent limiting factor for treatment continuity in cancer patients, as, after its occurrence, the peripheral venous catheter should be immediately removed(1). Depending on the extent of the inflammatory process established at the venipuncture site, the vascular endothelium suffers irreversible injuries, such as phlebosclerosis, so that the venous segment cannot be used for new intravenous infusion punctures, nor even for simple blood collection(2). Thus, phlebitis prevention, control of its evolution after its occurrence and reversal of its characteristic inflammatory signs are needed, mainly in patients whose venous network is already very sensitive as a result of antineoplastic chemotherapy. Conventionally, as a nursing intervention for phlebitis treatment, topical lukewarm compresses are indicated to reduce the local inflammatory process. Depending on the phlebitis intensity, however, applying compresses alone is not enough to improve the inflammatory process, leading to the need to for medical prescription of systemic anti-inflammatory agents, which constitutes an additional factor for the immune system commitment of cancer patients. Therefore, it is fundamental for Brazilian nursing to start to research, within its professional competency area, on alternative and more effective phlebitis treatment forms, using phytotherapy for example. The Federal Nursing Council establishes and recognizes this practice, through COFEN Resolution 197/1997(3); as a specialty and/or qualification for nursing professionals. According to the "Guia para a realização de estudos de toxicidade pré-clínica de fitoterápicos"(4) [Guide for preclinical phytotherapeutic drug toxicity studies], any and all phytotherapeutic or vegetal drugs under analysis should obligatorily be submitted to toxicological tests. Toxicity studies need to be conducted with standardized samples of the phytotherapeutic or vegetal drug based on which it is produced. According to the same standard, toxicity should be assessed after the user's exposure to a single or fractionated dose, which should be administered to the patient within 24 hours. The Lista de Registro Simplificado [Simplified Registry] by the Brazilian Health Surveillance Agency(5) already contains Chamomilla recutita (L.) Rauschert (Asteraceae), so that proving efficacy and safety is not needed. Infusion is not considered a pharmaceutical form yet in Brazil, however - as opposed to what happens in other countries like Germany, which considers C. recutita infusion a pharmaceutical form. This research aimed to estimate the ideal dose, for anti-inflammatory purposes, of C. Recutita floral capitula infusion, in patients with phlebitis due to peripheral intravenous infusion of antineoplastic chemotherapy, as well as to assess the toxicity of this infusion in human beings. Besides, the vegetal species used was especially grown, standardized and characterized with a view to certification for medicinal use and later validation of its therapeutic efficacy and safety, as a secondary study goal. Method Cultivation, standardization and characterization of C. recutita "Cultivar Mandirituba" C. recutita seeds were used for planting, donated by Empresa de Assistência Técnica e Extensão Rural do Paraná (EMATER-PR) [Paraná State Rural Technical Assistance and Service Company]. Organic planting was followed, in an aviary bed, located in a nursery in the Medicinal Plant Garden of the Federal University of Mato Grosso do Sul (HPM-UFMS). Sowing occurred in May 2005. During the cultivation cycle, weed control, performed with the help of a hoe, and irrigations through sprinklers were done whenever necessary. No pesticides were used directly on the plants to control plagues or diseases. Manual harvesting occurred in September 2005 by technicians from HPM-UFMS. The drying of the collected floral capitula was done in a forced-air circulation glasshouse with temperature ranging between 36º ± 2ºC, to constant mass, resulting in 56.57 million ha-1; equivalent to 8kg of floral capitula of C. recutita. After drying, the floral capitula of C. recutita were stored in lidded glass pots and kept refrigerated. The physical-chemical evaluation of C. recutita inflorescences was done in accordance with the methods described in Farmacopéia Brasileira(6) and USP 28(7). A sample of about 500.0 g was grinded and submitted to physical-chemical characterization, including identification, purity and integrity tests and marker dosage. This dosage consisted in the quantification of total flavonoids in the floral capitula and α-bisabolol in essential oil. After being submitted to the describe cultivation, harvesting, drying and storage processes, the dry floral capitula of C. recutita were destined for laboratory analysis, when the excellent quality of the raw material was verified, as evidenced in the physical-chemical characterization of the sample (Table 1). Total flavonoid content in the floral capitula of chamomile was determined by 425 nm spectrophotometry, according to an adapted method described in literature(8-9). Total flavonoid concentration (expressed in quercetin) was calculated per 100.0 g of the sample. The same procedure was applied to determine total flavonoid contents in the four infusion dosages (Table 1), with a view to better characterization and comparison with future study data. α-bisabolol content was determined by gas chromatography with flame ionization detector (GC-FID). Therefore, the essential C. recutita oil was previously extracted, using hydrodistillation with a Clevenger apparatus. Triple analysis was performed, using an analytic α-bisabolol curve ranging from 200.0 to 1000.0 μg/mL, using piperonal as internal standard. Finally, the main constituent elements present in the essential oil were identified, using gas chromatography with mass detector (GC-MD). α-bisabolol content in the essential oil could be quantified through the equation of the straight line obtained from the analytic curve with internal standardization (R = 0.9993), corresponding to 10.9% m/m. According to GC-MD analysis of the essential oil, five major peaks of the plant's main active principles could be clearly identified, which should be highlighted: α-bisabolol oxide B (19.6%); α-bisabolone oxide (5.2%); α-bisabolol (9.0%); camazulene (1,3%); α-bisabolol oxide A (40.7%), besides spathulenol, β-elemene, limonene oxide, β-farnesene and d-nerolidol. Clinical Phase A dose response curve trial was carried out, in which the therapeutic efficacy of different C. recutita infusion doses was analyzed and compared in cancer patients with phlebitis deriving from peripheral intravenous infusion of antineoplastic chemotherapy, looking at the anti-inflammatory potential. Dose response curve studies demonstrate the relation between the dose (concentration) of an administered drug and the produced tissue response or effect, permitting knowledge on the adequate dose based on the wanted and unwanted effects obtained during the clinical application(10). The research was carried out at a public hospital in the Federal District, which is a tertiary referral institution for cancer care and offers 18 hematology and clinical oncology beds. The sample comprised 25 patients who formally agreed to participate by signing the Informed Consent Term (ICT). All patients had been diagnosed with degree-2 phlebitis according to the staging proposed by the Infusion Nursing Society(11) and were between 20 and 30 years old. Thirteen participants were women and 12 men, whose white blood cell count showed adequate normality levels for neutrophil (2000 - 7500/μl) and monocyte (100 - 800/μl)(12) counts, medically diagnosed with Acute Myeloid Leukemia (AML), submitted to the first, second or third cycle of the chemotherapy protocol IDA + ARA-C (idarubicin and cytarabine), through peripheral intravenous infusion. The exclusion criteria were the patients' affirmative response when asked about previous adverse reactions to chamomile or any plant in the Asteraceae or Compositae family, medical prescription of systemic or topical anti-inflammatory drug on the phlebitis site and refusal to continue participating in the study. The primary researcher established the criterion to allocate the subjects to the groups as follows: the first selected patient was automatically allocated to trial group A, the second to group B, the third to group C, the fourth to group D and the fifth to the control group. This process was repeated until 25 patients had been allocated. Data were collected between September and December 2005. Patients who complied with the selection criteria were allocated in five groups, one of which was the control group. A 20 cm2 cotton compress was used for the intervention, moistened with the C. recutita infusion when applied in the trial groups (Table 1) or with lukewarm water in the control group. In all groups, temperature was set at 38 °C. The graphs showing the dose-response curve are semi-logarithmic(10); with the dose axis showing the drug concentration in exponential progress. Hence, in this study, the researchers took care to establish the following dose concentrations, specified in Table 1. After removing the peripheral venous device, the moistened compress was applied on the phlebitis evidenced in the subject's upper limb, three times per day (morning, afternoon and night), according to the dose established in the group the patient had been allocated to, i.e. trial group A, B, C, D or control. As soon as the compress had been applied, the limb was wrapped in transparent PVC film to preserve local heat. Compress application time was set at 20 minutes for all groups and compresses were changed every 5 minutes. Only the main researcher applied the intervention in all patient groups. After the phlebitis diagnosis, the application time of the first compress was registered. The treatment site was assessed daily at three distinct times: at 8, 13 and 19 hours, with a view to uniform readings. The intervention was continued until the complete disappearance of the erythema, considered the main outcome. The erythema was chosen as the parameter to assess the inflammatory regression as this is a classical sign of any inflammation and an objective data, present in degree-2 phlebitis (local pain, erythema and/or edema), according to the staging proposed by the Infusion Nursing Society(11). Thus, the erythema regression time constituted a safe parameter to monitor the inflammation, offering the advantage that nursing professionals know and identify clinical phlebitis staging criteria very well, entailing additional security for assessment precision. To measure to erythema, transparent paper ruled in one-centimeter squares was used, based on which the erythema area was calculated very precisely, so that any alteration in the dependent variable could be identified. Like the subject allocation procedure to the respective groups, the same researcher performed the intervention and evaluation. Toxicity was investigated through visual assessment of the application site, looking for any signal that would indicate any reaction to the infusion, and also for symptoms. For toxicological evaluation, a compress was applied with the dose that presented the best dose-response effect in four other subjects with the same characteristics as the subjects but who did not present phlebitis, in compliance with (ANVISA) [National Health Surveillance Agency] Resolution RE Number 90, issued on March 16th 2004 - about toxicity evaluation of phytotherapeutic interventions - which suggests additional toxicity evaluation in healthy individuals(3). One-way variance analysis (ANOVA) was used for statistical analysis of the results, followed by multiple comparison test - Bonferroni test(13-14); using Graph Pad PrismI software, demo version, 5.0 for Windows. Significance was set at 5% in all tests. Approval for this research project was obtained from the Institutional Review Board of the Federal District Health Secretary, opinion number 062/2004. Results Intergroup comparison showed a statistically significant difference in the groups that received 2.5% and 5% infusions (i.e. corresponding to total flavonoid contents of 0.04 and 0.08 mg/mL, respectively) regarding the phlebitis regression time in comparison with the other groups (concentrations of 1.25% and 10%) and the control group (Figure 1) Erythema regression time in the study sample ranged between 19 and 120 hours for different dose concentrations used. The group in which the 2.5% concentration compress was used showed the shortest regression times: 19 and 24 hours (Table 3). The dose-response curve (Figure 2) evidences that the average phlebitis regression time was shorter for the 2.5% concentration group (mean = 29.2h, standard deviation = 8.98), followed by the 5% concentration group (mean = 38.8h, standard deviation = 17.47), and longer for the 1.25% (mean = 57.8h, standard deviation = 11.10) and 10% concentration groups (mean = 49.4h, standard deviation = 4.67). Mean regression time in the control group was 110.4h and standard deviation 13.15. As for toxicity, moderate to severe itching was reported on the left forearm of one of the patients allocated in trial group C, whose compress had been applied on the anterior front forearm. As the itching expanded, the transparent PVC film used on the entire forearm could have caused this. The subject was forwarded to the medical team, medicated with an anti-histaminic drug and showed complete regression of the itching within two hours. Local treatment was continued with warm water compresses at 38° C until the complete regression of the erythema. With regard to toxicity evaluation in subjects without phlebitis (n=4), no manifestations of hypersensitivity reactions occurred, nor reports of burning, itching or any other symptoms related with possible hypersensitivity to the drug. Discussion It is fundamental to determine the total flavonoid contents when assessing a plant's quality, especially in studies that use flavonoids for therapeutic purposes(15). Tests involving about 100 samples of 12 chamomile varieties cultivate in identical conditions showed flavonoid contents ranging between 1.0 and 2.6%, while twenty other samples of different origins showed total flavonoid content levels varying between 0.3 and 3.0%(15). The sample used in this study showed 2.5% m/m of total flavonoids, in line with previously found results. As for α-bisabolol content in essential oil, the level identified in the sample (10.9% m/m) surpassed literature recommendations according to the used temperature, which is 7%(15). Qualitative analysis of the plant's active principles confirmed available literature data about the chemical composition of C. recutita, describing terpenes (α-bisabolol, bisabolol oxide A and B, camazulene and sesquiterpenes), flavonoids (apigenin-7-glucoside, luteolin, quercetin), coumarins (umbelliferone) and steroids(16). It should be reminded that these elements, terpenes, steroids and sesquiterpenes exert anti-inflammatory effects, generally inhibiting the classical route of the complement system, interfering, in turn, in arachidonic acid metabolism(17). With regard to the clinical phase, research subjects in all groups were comparable, as the main confounding factors, including age, sex, white blood cell count and baseline disease were similar. Among the 25 participants, those in group A (dose 1.25%) showed the longest inflammation process regression time (range: 48 - 72h), while those in groups B and C showed the shortest regression time (range: 19 - 48h). Group D showed a longer regression time than groups B and C because, despite a higher dose - 40 g of floral capitula of C. recutita - the compress could not be totally moistened with the quantity of solvent used. This quantity did not need to be adjusted though, as lower doses had already demonstrated an excellent effect in terms of regression time of the inflammatory process. Other clinical trials have confirmed the anti-inflammatory effect of C. recutita in radiation dermatitis, through the use of ointments with chamomile extract (Kamilosan®)(18); in mucositis, through oral solution (Kamilosan® Solução Oral)(19); in contact dermatitis and eczema, through ethanolic extract(20-21); showing even superior efficacy results when compared with steroidal and non-steroidal anti-inflammatory drugs(21). Researchers(22) have assessed the efficacy of medical plant infusions (chamomile, salvia and calendula) for topical application in the treatment of Hand-Foot Syndrome resulting from intravenous capecitabine infusion, an antineoplastic chemotherapy drug used in breast cancer patients. The sample comprised 11 patients who immersed their hands and feet into the infusion daily. Significant regression of the inflammatory process was found in all cases. As for the dose, literature recommends concentrations between 3 and 10% for external use in compresses(23-24). It was observed, however, that with 2.5% concentrations, results were as satisfactory as with 5% concentrations, to the extent that the shorted regression time of the inflammation process was obtained in two patients, i.e. 19 and 24 hours. Both concentrations showed statistically significant results when compared mutually (p<0.05) and with the control group (p<0.001). When compared with the other concentrations (1.25% and 10%), the 2.5% dose showed a statistically significant difference (p<0.05), while the 5% dose showed no statistically significant difference with the other doses. Therefore, the researchers decided to choose the 2.5% concentration (10 g/400 mL) for floral capitula infusions of as the standard dose for this study, although literature recommends using concentrations between 3 and 10% for compresses. This small difference of -0.5% between the result obtained in the dose-response curve and the concentration recommended in literature (at least 3%) can be attributed to the excellent quality of the test sample, of Brazilian origins. Besides, it should be highlighted that literature itself shows different variations in terms of quantity definitions and even measurement units. The US Pharmacopeia, for example, indicates the use of two dessert spoons for external use, equivalent to approximately 6g of dry floral capitula of C. recutita in 250 mL of water(25); i.e. 2.4%, which is basically the same standard dose found in this research phase. The same source highlights that concentrations between 3 and 10% are indicated for ointments and gels. It is also important to highlight that using less grams of floral capitula with better results in terms of time for phlebitis regression generates a better cost-benefit relation and, hence, greater advantage for consumers, due to the obvious economy of the main resource. Itching was reported in one of the patients allocated in trial group C, with a 5% infusion concentration. The reported hypersensitivity reaction - itching - occurred across the subject's left forearm, who classified it as moderate to intense when the researcher asked about the intensity, although the compress had only been applied on the anterior front middle third of the left forearm. With regard to this episode, although allergic reactions to C. recutita are quite rare, these can happen, to the extent that one of the exclusion criteria was exactly the patient's affirmative response as to any adverse reaction to chamomile or any plant from the Asteraceae or Compositae family. It should be clarified that the sites where the compresses were applied, in the trial as well as in the toxicity control group, were assessed for an additional two days after the application, with a view to investigating late signs and symptoms of toxicity. This was not verified in any of the other subjects who accepted to participate in the research. As for the itching in one of the sample subjects, the symptom regressed within 72 hours, without the need for any medication intervention. Conclusion The standardization of vegetal raw material, ranging from the selection of the species, seeding, cultivation, harvesting, drying, storage and quality assessment is fundamental, mainly when used for therapeutic purposes, like in the case of this research. Based on the results, it can be inferred that, at α = 5%, the C. recutita infusion presents minimal or almost zero toxicity for topical application. This study also demonstrated that the 2.5% concentration for floral capitula infusion of C. recutita, when applied for anti-inflammatory purposes in case of phlebitis deriving from peripheral intravenous chemotherapy infusion, is as effective as the concentration suggested by literature, i.e. between 3 and 10%. This research contributes to the innovation of clinical nursing practice, as it suggests a treatment alternative for phlebitis deriving from peripheral intravenous infusion during antineoplastic chemotherapy. Moreover, theoretical support is provided regarding the methods to adopt for the clinical use of phytotherapeutic drugs. References 1. Machado AF, Pedreira MLG, Chaud MN. Adverse events related to the use of peripheral intravenous catheters in children according to dressing regimens. Rev. Latino-Am. Enfermagem. Maio-junho 2008; 16(3):362-7. [ Links ] 2. Reis PED, Capucho CR, Vasques CI, Carvalho EC. Efeitos adversos identificados em local de infusão intravenosa periférica por drogas quimioterápicas. Cienc Enferm. 2008; 14(2):55-64. [ Links ] 3. Conselho Federal de Enfermagem. Resolução COFEN 197/1997 [acesso em: 23 setembro 2009]. Disponível em: [ Links ] 4. Ministério da Saúde (BR). Agência Nacional de Vigilância Sanitária. Resolução RE n. 90, de 18 de março de 2004. Determina publicação do "Guia para a realização de estudos de toxicidade pré-clínica de fitoterápicos". Diário Oficial da República Federativa do Brasil, Brasília (DF): Imprensa Oficial; março 2004. Seção 1. [ Links ] 5. Ministério da Saúde (BR). Agência Nacional de Vigilância Sanitária. Resolução de Diretoria Colegiada (RDC) n. 89, de 16 de março de 2004. Determina a publicação da Lista de Registro Simplificado de Fitoterápicos junto ao Sistema de Vigilância Sanitária. Diário Oficial da República Federativa do Brasil. Brasília (DF): Imprensa Oficial; março 2004. Seção 1. [ Links ] 6. Farmacopéia Brasileira. 4a. ed. São Paulo: Atheneu; 1996. Parte 2, Fascículo 1. [ Links ] 7. . United States Pharmacopeia (USP) 28. 28ª. ed. Rockville:United State Convention; 2005. [ Links ] 8. Dowd LE. Spectrophotometric Determination of Quercetin. Anal Chem 1959; 31(7):1184-7. [ Links ] 9. Jay M, Gonnet J, Wollenweber E, Voirin B. Sur L'analyse. Qualitative des Aglycones Flavoniques dans Une Optique Chimiotaxinomique. Phytochemistry 1975; 14:1605-12. [ Links ] 10. Page C, Curtis M, Sutter M, Walker M, Hoffman B. Farmacodinâmica e a quantificação da droga. In: Page C, Curtis M, Sutter M, Walker M, Hoffman B. Farmacologia integrada. 2ª ed. Barueri (SP): Manole; 2004. p. 57-68. [ Links ] 11. Infusion Nursing Society. Infusion Nursing Standards of Practice. J Infusion Nurs. 2006; 29(1):S58-60. [ Links ] 12. Coutinho V, Coutinho MA. Análise do exame hematológico. In: Zago MA, Falcão RP, Pasquini P. Hematologia: fundamentos e prática. São Paulo (SP): Atheneu; 2001. p. 1081. [ Links ] 13. Armitage P, Berry G. Statistical methods in medical research. 3ª ed. Boston: Blackwell Scientific Publications; 1994. [ Links ] 14. Hamilton LC. Statistics with STATA. Califórnia: Thomson - Brooks/Cole; 2004. [ Links ] 15. Franke R, Schilcher H. Chamomile: industrial profiles. New York (NY): Taylor and Francis Group; 2005. [ Links ] 16. Szelenyi IO, Thiemer K. Pharmacological experiments with compounds of chamomile: Experimental studies of the ulcerprotective effect of chamomile. Planta Med. 1979, 35: 218-27. [ Links ] 17. Schulz V, Hänsel R, Tyler VE. Fitoterapia racional: um guia para as ciências da saúde. 4ª ed. São Paulo(SP): Manole; 2002. [ Links ] 18. Maiche AG, Grohn P, Maki-Hokkonen H. Effect of chamomile cream and almond ointment on acute radiation skin reaction. Acta Oncol. 1991;30(3):395-6. [ Links ] 19. Carl W, Emrich LS. Management of oral mucositis during local radiation and systemic chemotherapy: a study of 98 patients. J Prosthet Dent. 1991;66(3):361-9. [ Links ] 20. Santoro M. Efeito terapêutico do extrato etanólico das flores de camomila em base cremosa no tratamento da dermatite das fraldas - estudo multicêntrico. Rev Paul Pediatr. 1998;16(2):69-76. [ Links ] 21. Aertgeerts P, Albring M, Klaschka F, Nasemann T, Patzelt-Wenczler R, Rauhut 1985;60(3):270-7. [ Links ] 22. Kern E, Schmidinger M, Locker GJ, Kopp B. Management of capecitabine-induced hand-foot syndrome by local phytotherapy. Wien Med Wochenschr. 2007;157(13-14):337-42. [ Links ] 23. Blumenthal, M. The complete german commission E monographs - therapeutic guide to herbal medicines. Boston: American Botanical Council; 1998. [ Links ] 24. WHO. WHO monographs on selected medicinal plants. Genebra: World Health Organization; 1999. [ Links ] 25. PDR for herbal medicines. 2ª ed. Montvale: Medical Economics Company; 2000. [ Links ] Corresponding Author: Emilia Campos de Carvalho Universidade de São Paulo Escola de Enfermagem de Ribeirão Preto Departamento de Enfermagem Geral e Especializada Av. dos Bandeirantes, 3900 Campus Universitário CEP: 14040-902 Ribeirão Preto, SP, Brasil Received: Oct. 7th 2009 Accepted: May. 24th 2010 1 Paper extracted from Doctoral Dissertation "Uso tópico terapêutico da Chamomilla recutita em flebites decorrentes de terapia intravenosa periférica",.

SMART Business Objectives This is ‘How To Business Strategy’ covers the art of defining your business objectives. I’m not so keen on the term SMART Objectives only because it is so over used that I don’t think it helps that much. This template below is more definitive. Have a look then have a go … Feel free to request the templates laura@thehiddenedge.co.uk. I am happy to share. 1. Recognise the importance of the Business Vision, the Mission and the Business Values to business objectives 2. Identify the 3-5 critical success factors for your business and the key performance indicators in relation to those 3. Use the following template to create strategic objectives and specific objectives for projects or teams. a. Start with an action verb b. Describe the activity c. Identify the current position – where you are now d. Specify where you would like to be – your intended position e. Give yourself a deadline >

Pope pius xii essay Pius xii and the holocaust essaypius xii has often been portrayed as the pope who kept silent during the holocaust. In his own words from the book relevant to this essay, hitler's pope: that pope pius xii saved 800,000 the persecution of the catholic church in the. Pius xii and the third reich on studybaycom - after coming to power in 1933, online marketplace for students. Pope pius xii essays: over 180,000 pope pius xii essays, pope pius xii term papers, pope pius xii research paper, book reports 184 990 essays, term and research. Pope pius xii in the second world war pope pius xii sat on the throne of st peter in this essay has been adapted by mary ball martinez from a section. 14, 2013 pope pius xii and the holocaust pope pius xii was the pope during world war ii and during the nazi holocaust where adolf hitler’s nazis murdered. Essays research papers - pope pius xii and the jews. Free essay: the germans were likewise displeased with the reigning pontiff, pius xi, who showed himself to be a unrelenting opponent of the new german. Cornwell's ''hitler's pope: the secret history of pius xii'' was criticized for minor errors and its sensationalist title. Pope pius xii faith formation program (project book and you must participate in a peer pope pius xii board of review and then submit your application for. Requiescat in pace in memory of the last true pope (so far) pope of the death of the last known true pope, his holiness pius xii an essay entitled “sede. Pope pius xii's neutrality essay 1964 words | 8 pages if the bvp could be diminished, the nazi party would be able to grow and eventually gain complete control of. White papers and essays special contact pope pius xii and the holocaust home / pope pius xii and the holocaust / pope pius xii and pius xii was hated by. - Pope pius xii, the holocaust, and the identity question in the controversy caused by pope pius xii it is not the purpose of this essay to revisit the. - Home / white papers and essays / the church and the holocaust / “60 minutes” on pope pius xii previous next who complained about pope pius xii’s “silence. The venerable pope pius xii, born eugenio maria giuseppe giovanni pacelli (march 2, 1876 in rome, italy - october 9, 1958 in castel gandolfo, italy), served as the. Pope pius xii: hitler’s pope the holocaust was a devastating time, which caused an unbelievable number of deaths, so much pain, agony, and turmoil to so many. Why pius xii chose not to take a strong stance against the holocaust (back to top) as recently stated, the pope knew that he was powerless against hitler.

© IWM Art.IWM PST 2794 2794 - Hengst, Oswald (Undefined) Wagner'sche K K Universitäts-Buchdruckerei, Innsbruck (printer) Centralbank der Deutschen Sparkassen (publisher/sponsor) - Production date - 1917 - Place made - Austria-Hungary - Materials Support: paper medium: lithograph - Dimensions Support: Height 952 mm, 626 - Catalogue number - Art.IWM PST 2794 Object associations - Associated people and organisations - - Associated places - Associated subjects - Associated keywords - Associated themes

Despite their loyal attitude, some dogs are unfortunate as they experience cruelty at the hands of their owners. Max, a two-year-old Rottweiler and Labrador mix, is no stranger to this. Just recently, the pooch was subjected to unthinkable cruelty. His former owners took him out of their house and shot the dog twice with a shotgun. None of the shots were fatal, but the previous heartless owner of the dog left Max to die. Good thing, there was a stranger who passed by outside the house of Max and noticed the pooch. During this time, the dog was already tied on the fence and still looking in pain. The stranger pitied the situation of the dog and called the Humane Society to report the incident. Two officers of the Humane Society of Jackson County responded to the report. Deputy Sheriff Alan Hughes and Humane Officer Teresa Hagger went to the place where Max was. They saw that the dog was struggling from afar, so they hastened their rescue. Max seemed to know that he was going to be rescued because he was not aloof with the two officers. Instead, he just let the two officers untangled from where he was tied. The two officers immediately brought the pooch to the animal care to be treated. Once the dog was already free from any harm, the two officers brought Max to an animal care unit and renamed him to Fisher. The reason for the rename is for the dog not to be traced by his former owners. Fisher is still recovering from the injuries and trauma he incurred from the incident. He temporarily lives in Jackson County Animal Shelter, where from time to time, he receives visitors. As soon as the dog recuperates physical and mentally, the shelter will put the dog on their adoption list. Update on Fisher he has a lot of swelling in his jaws and neck. But making slow progress. He is being a good boy and… Posted by Jackson County Animal Shelter on Monday, December 23, 2019 Credits to Jackson County Animal Shelter.

Most stock investors don't pay a lot of attention to the currency markets. But for more than a year, the U.S. dollar has been steadily losing value against most of its foreign counterparts, and the move has had plenty of ramifications -- not just for the foreign exchange markets, but for corporations around the world as well. Now, though, it looks like the dollar's plunge may be coming to an end. That leads to an obvious question: If the dollar is poised to rise from here, how will it affect your investments? What goes down must go up? It's easy to understand why the dollar has been under pressure in recent years. Rock-bottom interest rates make the currency unattractive to fixed-income investors seeking substantial returns from their investments. High budget and trade deficits should theoretically lead to currency weakness over the long haul. And with the loss of the U.S. government's AAA credit rating, faith in the nation's ability to resolve its differences and get back on a sustainable financial track seems lower than ever. But despite the negative attention that the dollar has gotten, the same arguments hold true for many other currencies, and that realization may be driving gains. In particular: - The Swiss franc plunged after the Swiss National Bank made an amazing intervention in the foreign exchange markets, essentially pegging the franc to the euro and lopping off more than 10% of its value as a result. - Increasing concerns that Greece will default soon have pushed the euro down, and because the euro is the biggest component of the widely followed Dollar Index, that index is finally showing signs of potentially reversing a months-long downtrend. - Moves from emerging markets like Brazil to contain red-hot currency swings seem finally to be working, as the Brazilian currency has given up some of its past gains. Of course, we've seen false alarms from past dollar up-moves that proved to be short-lived. But if this is the real deal, what's the best way to profit from a stronger dollar? What euro investors are doing One interesting answer comes from looking at what institutional investors outside the U.S. are doing. For instance, as Europe remains under pressure, you might expect European investors to run from the region entirely. But instead, investors are focusing on companies that are best poised to survive euro turmoil and profit from its weakness. Export-oriented megacaps Royal Dutch Shell (NYSE: RDS-A ) and Vodafone (Nasdaq: VOD ) , as well as drug companies Sanofi (NYSE: SNY ) and GlaxoSmithKline (NYSE: GSK ) , are based in Europe, but they do much of their business both in the U.S. and throughout the rest of the world. As a result, they'd benefit from a stronger dollar against the euro. Similarly, British American Tobacco (AMEX: BTI ) and Nestle are consumer favorites around the globe. Even though these countries do plenty of business in Europe and therefore could suffer from economic turmoil in their home region, having an international presence helps buffer them from the full impact of the problems. However, U.S. investors have to understand that the benefits of a weaker currency for the bottom lines of these companies will have an offsetting negative effect on their returns in dollar terms if the value of the euro continues to fall. Conversely, U.S. companies that do a strong business in Europe, such as Kraft Foods (NYSE: KFT ) and Johnson & Johnson (NYSE: JNJ ) , could see weakness if the dollar continues to strengthen. Even if their foreign revenues stay stable in euro terms, they'd translate to fewer dollars, causing sales growth to slow. Focusing on the long term But the better perspective to have about the dollar is whether any advance is likely to be lasting. Following the end of the financial crisis, the dollar rebounded sharply, only to lose all its gains and then some. Anyone who expected a longer-term recovery for the dollar got hurt badly. The fundamental problems that the U.S. is facing don't seem to be going away anytime soon. That suggests that any gain in the dollar might well simply be a good opportunity to load up on the investments that will eventually profit from a dollar decline. Some investors think that gold stocks are the best way to beat the currency markets. Read about a tiny gold stock that's digging up massive profits 6:01 PM, xetn wrote: I believe the dollar will find its intrinsic value when everyone decides that it is worthless (worth less) than the paper its not printed on. But, if you look at the history of fiat money, all the way back to the Roman Empire, they all eventually fail. Report this Comment On September 12, 2011, at 6:20 PM, AvianFlu wrote: The dollar will not plateau until at least 2 years after the debasement efforts cease. It takes time for currency debasement to work it's way through the system and result in price inflation. And something tells me that the debasement efforts are not over. But we'll see. What is clear is that we are not the only country working to actively debase our currency. So finding a safe haven is not particularly easy. Does one even exist anymore? Report this Comment On September 12, 2011, at 7:04 PM, soycapital wrote: If the dollar is on the way up better watch out short term stock market!

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ENGREF 19 avenue du Maine 75015 Paris Télécharger le fichier «Fokianos_may2012.pdf» (74.9 KB) Documents de cours : - Télécharger le fichier «Fokianos_CTSM.pdf» (196.4 KB) - Télécharger le fichier «Fokianos_JMVA.pdf» (752.6 KB) - Télécharger le fichier «Fokianos_NLPA.pdf» (636.3 KB) - Télécharger le fichier «Fokianos_PA.pdf» (278.3 KB) - Télécharger le fichier «Fokianos_STAPRO.pdf» (384.3 KB) In this course we will consider parametric and nonparametric estimation for processes that can be built by using some nonlinear functionals of Gaussian processes. We shall consider no only processes of real parameter but also random fields. The examples that we have in mind are: fractional diffusions, non isotropic Gaussian random fields and the estimation of their anisotropy, and estimation via functionals of level sets Documents de cours : - Télécharger le fichier «Leon1_may2012.pdf» (1.1 MB) - Télécharger le fichier «Leon2_may2012.pdf» (490 KB) Model based-drug development (MBDD) is accepted as a vital approach in understanding patient risk/benefit and attrition. At the core of MBDD lies Modelling and Simulation (M&S), a technology providing the basis for informed, quantitative decision-making. M&S facilitates the continuous integration of available information related to a drug or disease into constantly-evolving mathematical models capable of describing and predicting the behaviour of studied systems to address the questions researchers, regulators, and public health care bodies face when bringing drugs to patients. The mathematical models used for describing complex biological phenomena are complex: they are usually be based on (Ordinary, Partial, Stochastic...) Differential Equations. Furthermore, the statistical component of the model should be carefully taken into account, in order to properly describe the variability between patients of the response to a same treatment. Because of this complexity, new methods need to developed for parameter estimation, model assessment, model selection,... I will present several models (Pharmacokinetic/Pharmacodynamic, HIV dynamics, epilepsy ...) and some statistical tools that we have developed for these models and which are now widely used for practical applications. Nonlinear estimation in a nonstationary environment The talk consists of two parts. In the first part I will give an overview over nonparametric estimation and testing in nonstationary Markov time series using the splitting technique. The relationship to nonlinear cointegrating regression will be pointed out. Unlike the stationary case there could be a fundamental difference between regression and autoregression. In the second part I will look at some new results for parametric estimation for nonstationary time series. Again the Markov splitting technique is useful. This approach will be compared to an approach using local time. Télécharger le fichier «Tjostheim_may2012.pdf» (368.1 KB) Contact : thomas.ballesteros@u-cergy.fr ( thomas.ballesteros @ u-cergy.fr) Une table ronde sera organisée le 11 mai 2012 sur Paris pour exploiter les notions induites lors des cours dans une dynamique de recherche tant théorique qu’appliquée.

More items will be denied Forex, says CBN Governor The governor of the Central Bank of Nigeria, Godwin Emefiele, says more items will soon be denied foreign exchange from government institutions and Nigeria banking industry. Mr Emefiele also said that the bank will not go back on the directive of President Muhammad Buhari on food importation into the country. President Muhammad Buhari had on Tuesday in Daura, Katsina State, directed the Central Bank of Nigeria (CBN) to stop providing foreign exchange for importation of food into the country. Speaking with State House correspondents on the sidelines of the ongoing retreat for ministers designate at the Presidential Villa, Abuja, Monday, Emefuele also said that Nigeria will move to get a stay of action against the $9 billion judgment by a British court. A British Court had last Friday ruled that an engineering and project management company, Process and Industrial Developments Ltd., has the right to seize $9bn Nigerian assets. The ruling. On how far he has gone on the President’s directive, Emefiele said Mr President’s comment on the issuing of forex to people who import food items into the country, is in the logic of CBN’s management foreign exchange policies that was started since 2016. He said the directive is purely to strengthen the position of the CBN on food importation.